The Function And Molecular Mechanisms Of E-cadherin Ubiquitination Regulated By USP14 In EMT Of Breast Cancer Cells

Breast cancer is one of the malignant tumors that threaten the health of women worldwide.Breast cancer metastasis is the main cause of increased mortality of breast cancer.Therefore,to further study the molecular mechanism of breast cancer metastasis and to find new strategies to inhibit the process of small molecule drugs to effectively reduce the mortality rate of breast cancer have become a key issue in the treatment of breast cancer.There are few researches of USP14 on the invasion and migration of breast cancer.Epithelial–mesenchymal transition(EMT)provides a basis for metastatic invasion of tumors,and downregulation of E-cadherin is the marker of EMT.In our study,we found that knockdown USP14 protein expression and treatment with USP14 specific inhibitors resulted in significantly reduced migration and invasion ability of breast cancer cells.We then found that knockdown USP14 significantly inhibited the EMT process of breast cancer cells by cell morphological experiments and detection of expression of EMT related markers.By Western Blot techniques,it was clear that USP14 affected the migration and invasion ability of breast cancer cells by regulating E-cadherin expression.Finally,based on the characteristics of USP14 deubiquitinase,we used immunoprecipitation to detect the effect of USP14 on E-cadherin ubiquitination levels.As a result,it was found that K63 ubiquitination of E-cadherin increased significantly after knockdown or treatment with specific inhibitors to suppress USP14 function.In summary,we found that the down-regulation of the function of inhibiting USP14 can inhibit the ability of blocking the invasion and metastasis of breast cancer cells,and for the first time confirmed that USP14 affects cell metastasis function by regulating E-cadherin ubiquitination,providing new research directions ideas.